The goal of this work was to nondestructively measure glomerular (and thereby nephron) number in the whole kidney. Variations in the number and size of glomeruli have been linked to a number of renal and systemic diseases. Here we develop a robust magnetic resonance imaging (MRI) technique based on injection of cationic ferritin (CF) to produce an accurate measurement of number and size of individual glomeruli. High-field (19T) gradient-echo MR images of perfused rat kidneys after in vivo intravenous injection of CF showed specific labeling of individual glomeruli with CF throughout the kidney. We developed a 3D image processing algorithm to count every labeled glomerulus. MRI-based counts yielded 33,786+/-3,753 labeled glomeruli (n=5 kidneys). Acid maceration counting of contralateral kidneys yielded an estimate of 30,585+/-2,053 glomeruli (n=6 kidneys). Disector/fractionator stereology counting yielded an estimate of 34,963 glomeruli (n=2). MRI-based measurement of apparent glomerular volume of labeled glomeruli was measured to be 4.89x10(-4) mm(3) (n=5), compared to the average stereological measurement of 4.99x10(-4) mm(3) (n=2). The MRI-based technique also yielded the intra-renal distribution of apparent glomerular volume, a measurement previously unobtainable in histology. This work makes it possible to nondestructively measure whole-kidney glomerular number and apparent glomerular volumes to study susceptibility to renal diseases and opens the door to similar in vivo measurements in animals and humans.
Beeman, S. C., Zhang, M., Gubhaju, L., Wu, T., Bertram, J. F., Frakes, D. H., Cherry, B. R., & Bennett, K. M. (2011). Measuring glomerular number and size in perfused kidneys using MRI. American Journal of Physiology-Renal Physiology, 300(6), F1454 - F1457. https://doi.org/10.1152/ajprenal.00044.2011